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language
eng
Author
Hashimoto, Michio
Shahdat Hossain Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumoshi, Japan.
Abdullah Al Mamun Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumoshi, Japan.
Arai, Hiroyuki Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Description
The accumulation of amyloid β peptide1-42 (Aβ1-42) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ1-42 curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ1-42 were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ1-42. Computational analyses of the binding of DHA to Aβ1-42, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ1-42 fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.
Subject
Docosahexaenoic Acid
Alzheimer’s Disease
Amyloid Beta Peptide
Molecular Docking
In Silico
Drug Design
Protein Data Bank
Journal Title
Advances in Alzheimer’s Disease
Volume
5
Issue
2
Start Page
73
End Page
86
ISSN
2169-2459
ISSN(Online)
2169-2467
Published Date
2016-6-29
DOI
Publisher
Scientific Research Publishing (SCIRP)
NII Type
Journal Article
Format
PDF
Text Version
出版社版
OAI-PMH Set
Faculty of Medicine